ABSTRACT
OBJECTIVE To e xplore the research hots pots and development frontiers of ursolic acid in recent 20 years，and to provide reference for researchers in this field. METHODS Research literatures related to ursolic acid in Web of Science from Jan. ， 1，2002 to Dec. 31，2021 were collected ，and visualization analysis was performed on countries or regions ，research institutions ， authors，journals and keywords involved in the literatures using CiteSpace software ，to obtain the spatial and temporal distribution of ursolic acid and research frontiers. The research status and development frontier of ursolic acid were further analyzed by analyzing keywords co-occurrence ，keyword emergence ，keyword clustering ，etc. RESULTS & CONCLUSIONS Totally 3 528 valid papers were included in this study ，and the top three countries were China ，India and the United States. Analysis of publishing institutions showed that Chinese Academy of Sciences ，Univisity of Karachi and China Medical University were the top 3 research institutions in the list of publication amount. Analysis of published journals showed that Molecules （127 articles），Journal of Ethnopharmacology（90 articles），Journal of Agricultural and Food Chemistry （75 articles）had high number of literatures on ursolic acid. The analysis of keyword analysis showed that pharmacological effects ，such as antitumor activity of ursolic acid ， antioxidant activity ，antibacterial activity and anti-inflammatory activity ，are always the focus of the research ；the mechanism ursolic acid induced apoptosis ，oxidative stress and autophagy ，the research on ursolic acid signaling pathway ，drug delivery of ursolic acid nanoparticles were the research direction in the future.
ABSTRACT
OBJECTIVE：To explo re the potential molecular mechanism of ursolic acid in the treatment of osteoporosis （OP）. METHODS：TCMSP，PubMed database and UniProt database were used to screen potential targets of monomer compound ursolic acid. OP related target genes were searched with GeneCards database. The common target genes of component-disease were obtained by Venny 2.1 online mapping tool. The protein-protein interaction （PPI）network of component-disease common target genes was constructed by using STRING database ，and topological analysis was carried out ；the core target genes ，whose degree value was greater than the average degree value ，were screened. GO functional annotation and KEGG pathway enrichment analysis of component-disease common target genes were carried out by DAVID database. AutoDock Vina 1.1.2 software was used for molecular docking ，using protein encoded by the core target gene as receptor and ursolic acid as ligand. RESULTS ：A total of 55 ursolic acid related target genes and 4 273 OP related target genes were excavated ，with a total of 44 common target genes. PPI network with above common target genes included 44 nodes and 513 edges，with an average node degree of 23.3. There were 24 core target genes ，including VEGFA，TP53，IL6，CASP3. There were 340 GO functional items were enriched （corrected P＜ 0.05），including 263 biological processes （negative regulation of apoptosis ，etc.），25 molecular functions （protein binding ，etc.） and 52 cell components （cytosol，etc.）. There were 90 KEGG signaling pathways （corrected P＜0.05），such as tumor pathway ， hepatitis B pathway ，TNF signaling pathway ，viral carcinogenesis and phosphatidylinositol 3 kinase/protein kinase B （PI3K-Akt） signaling pathway. The binding energy between ursolic acid and 6 proteins encoded by core target genes such as TP53 was lower than －5 kcal/mol，which had strong binding activity. CONCLUSIONS ：The therapeutic effect of ursolic acid on OP may be achieved by regulating VEGFA，TP53，IL6，CASP3，JUN and other core target genes and acting on multiple key pathways such as cancer pathway ， hepatitis B and TNF signaling